Agmatine oxidation by copper amine oxidase: Biosynthesis and biochemical characterization of N-amidino-2-hydroxypyrrolidine

Paolo Ascenzi, Mauro Fasano, Maria Marino, Giorgio Venturini, Rodolfo Federico

Research output: Contribution to journalArticlepeer-review

Abstract

The product of agmatine oxidation catalyzed by Pisum sativum L. copper amine oxidase has been identified by means of one- and two-dimensional 1H-NMR spectroscopy to be N-amidino-2-hydroxypyrrolidine. This compound inhibits competitively rat nitric oxide synthase type I and type II (NOS-I and NOS-II, respectively) and bovine trypsin (trypsin) activity, values of Ki being (1.1 ± 0.1) × 10-5 M (at pH 7.5 and 37.0°C), (2.1 ± 0.1) × 10-5 M (at pH 7.5 and 37.0°C), and (8.9 ± 0.4) × 10-5 M (at pH 6.8 and 21.0°C), respectively. Remarkably, the affinity of N-amidino-2-hydroxypyrrolidine for NOS-I, NOS-II and trypsin is significantly higher than that observed for agmatine and clonidine binding. Furthermore, N-amidino-2-hydroxypyrrolidine and agmatine are more efficient than clonidine in displacing [3H]clonidine (= 1.0 × 10-8 M) from specific binding sites in heart rat membranes, values of IC50 being (1.3 ± 0.4) × 10-9 M and (2.2 ± 0.4) × 10-8 M, respectively (at pH 7.4 and 37.0°C).

Original languageEnglish
Pages (from-to)884-892
Number of pages9
JournalEuropean Journal of Biochemistry
Volume269
Issue number3
DOIs
Publication statusPublished - 2002

Keywords

  • Agmatine
  • Copper amine oxidase
  • Enzyme inhibition
  • N-amidino-2-hydroxypyrrolidine
  • Type 1 imidazoline receptor binding

ASJC Scopus subject areas

  • Biochemistry

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